The present invention relates to a sensor apparatus useful in detecting trace analytes in a sample, and more specifically determining the analyte""s biological or physical activity.
There exists a need for determining a variety of molecular properties that are important in determining a biological, a chemical, or a physical property or activity of a molecule and cataloging these properties so that they can be used to identify candidate lead molecules for a biological, chemical, pharmaceutical, or industrial application of interest.
Currently methods are used to screen potential drug compounds or biologics from a collection of molecules of interest (e.g., a library). Such methods use assay techniques that detect a specific activity based on a molecule""s binding affinity, enzymatic activity or other properties. Alternatively, lead compounds are generated by computational methods, wherein the molecules that possess certain desirable properties are defined by shape, dipole moments, surface area, solubility, vapor pressure, hydrophobicity, hydrophilicity, antigenicity and other physical properties. These chemical-physical properties are then defined and used to computationally narrow lead compounds to a manageable subset which are then analyzed further by additional screening techniques designed to measure a specific activity in vitro or in vivo by using additional high throughput screening techniques.
Generation of lead compounds is important because not only does it allow for exploration of a wider range of potential pharmaceutical agents, but it also offers opportunities for construction of follow-up libraries that focus on the molecular characteristics represented by these lead molecules. This in turn is performed to provide yet more leads with the desired pharmaceutical activity eventually with the hope of finding a candidate suitable for clinical use.
The present invention provides a method for identifying a specific activity, structure or function of a molecule of interest based on a sensing device. The sensing device includes an array of sensors responsive to a molecule""s physical, chemical, or biological characteristics. The differentially responsive sensors can be optical sensors, resonance mechanic frequency sensors, and/or electrical sensors to name a few. Other sensors and arrays are known to those of skill in the art. For example, in one embodiment the sensing device includes a chemical sensor comprising first and second conductive elements (e.g. electrical leads) electrically coupled to a chemically sensitive resistor which provides a selective electrical path between the conductive elements. The resistor comprises a plurality of alternating non-conductive regions (comprising a non-conductive material) and conductive regions (comprising a conductive material) in series. The electrical path between the first and second conductive elements is transverse to (i.e., passes through) a plurality of alternating non-conductive and conductive regions. In use, the resistor provides a change in resistance between the conductive elements when contacted with an analyte or molecule which interacts with the non-conductive region. The non-conductive region can be made of any material designed to interact or bind to a class, genus, or specie of analyte.
The disclosure provides a method and device for identifying a specific activity, structure or function of an analyte or molecule of interest. The method uses a sensing device to produce a characteristic experimental pattern generated by a plurality of differentially responsive sensors. The pattern has information on the desired molecular properties for a molecule or analyte of interest. A response pattern is produced for each member of the library. These patterns are then stored and associated with the library. The library contains patterns for molecules having a desired or known property or activity.
In one embodiment, a method is provided for screening samples for a specific activity or structure by measuring outputs of a plurality of chemically-sensitive resistors, each resistor comprising a conductive material and a non-conductive material; using results of said measuring to obtain a signal profile, relating to a change in resistance in the plurality of resistors; and comparing the signal profile to a previously-obtained signal profile indicating a standard sample having a specific activity, wherein the signal profile is indicative of a specific activity or a specific structure.
The disclosure additionally provides a screening system that includes a sensor array comprising a plurality of differentially responsive sensors, each sensor capable of providing a signal corresponding to the sensors interaction with a molecule of interest. A measuring device detects the signal from each sensor and arranges them into a signal profile representing a molecule""s characteristics (e.g., activity, structure, or function). A computer then compares the signal profile to determine the molecule""s activity. Preferably, the computer has a resident algorithm for comparing the signal profile(s).
For example, in one embodiment, a sample screening system is provided, the system including a sensor array comprising at least first and second chemically-sensitive resistors, each chemically-sensitive resistor comprising a mixture of non-conductive organic polymer and conductive material compositionally different than said non-conductive organic polymer, each resistor providing an electrical path through said mixture of non-conductive organic polymer and said conductive material, a first electrical resistance, when contacted with a first chemical analyte at a first concentration and a second different electrical resistance when contacted with a second analyte, wherein the difference between the first electrical resistance and the second electrical resistance of the first chemically-sensitive resistor being different from the difference between the first electrical resistance and the second electrical resistance of the second chemically-sensitive resistor; an electrical measuring device electrically connected to the sensor array; and a computer wherein the electrical measuring device detects the first and second electrical resistance in each of the chemically-sensitive resistors and the computer assembles the resistance into a sensor array signal profile, wherein the computer is operative to compare the signal profile to a signal profile obtained from a standard sample having a specific activity, wherein the signal profile is indicative of a specific activity or a specific structure.